Gram-negative Bacterial Infection
Throughout the world, sepsis caused by infection with Gram-negative bacteria is one of the major causes of death. Gram-negative bacteria are ubiquitous in the environment, and are present in the air, water, food, and are present in particularly high concentrations in the intestines. The surface of the skin is coated with Gram-negative bacteria and many skin infections are caused by these organisms. Because of their widespread distribution these bacteria cause opportunistic infections in association with other afflictions. For example, it is widely believed that sepsis is the most common cause of death in hospitals, and is particularly associated with conditions such as cancer, traumatic injury, and burns. A major cause of death in association with burns on the skin is infection and sepsis caused by gram-negative Pseudomonas organisms. Most urinary tract infections are caused by Gram-negative organisms. Individuals who are weakened by chronic diseases, or who have massive traumatic or burn injuries, or who have penetrating injuries of the intestines, are particularly at risk for developing life-threatening Gram-negative sepsis. Gram-negative infections that cause diarrhea are one of the major causes of death in infants.
The normal treatment of Gram-negative sepsis is by the administration of antibiotics that are active against sensitive organisms. The widespread use of such antibiotics has led to the continuous emergence of resistant strains of organisms and this has limited the effectiveness of antibiotic treatment. In addition, treatment often depends upon prompt administration of the appropriate antibiotic, but definitive laboratory tests to prove that the organism is sensitive to the antibiotic and that the optimally potent antibiotic is being used normally involves isolation and growth of the Gram-negative organism and inhibition by candidate antibiotics. Sensitivity tests normally require at least 1-2 days to perform, and because of urgency of many infections inadequate or suboptimal antibiotic therapy is often employed.
Immunotherapy with Lipid A
Suboptimal antibiotic use is one of the major factors responsible for emergence of antibiotic-resistant organisms. A new strategy of immunotherapy has been developed for the treatment of Gram-negative sepsis. This technique involves the administration of monoclonal (or polyclonal) human antibodies having specificity against lipid A. The monoclonal or polyclonal antibodies to lipid A that are used for immunotherapy are given by intravenous administration in individuals who have sepsis, and are usually used only when a relatively large infection has already become established. These individuals are frequently already in a toxic condition that renders the treatment by immunotherapy more difficult.